The Integrated Microscopy Resource has two prime objectives: to develop new instrumentation and techniques that extend the capabilities of both optical and electron microscopy and to provide a national resource for advanced microscopy for the biomedical community. The research into new specimen preparation techniques and the development of new microscopes being undertaken at the IMR are driven by the needs of key avenues of scientific investigation and the availability of new technology. The main focus at the IMR is the development of new techniques and instrumentation for in vivo imaging and optical experimental intervention. In addition, the IMR has a large commitment to electron microscopy, both as a high-resolution correlative adjunct to in vivo studies and also in its own right as an indispensable tool for obtaining high resolution structural information. We are proposing seven projects for pursuit in the next grant cycle. l) The development of new high-performance photodetectors for in vivo imaging that provide spectral and lifetime information. These detectors will enable full use to be made of the plethora of optical probes now available to the biologist. 2) To develop a high-speed multiphoton imaging system to enable fast events such as calcium transients to be captured by in vivo imaging. 3) To develop new probes that facilitate multiple labeling in the electron microscope and probes that can be used for integrated microscopy. 4) To develop techniques for multiphoton activation of caged probes to enable high spatial resolution to be achieved for this technique. 5) To investigate the causes of photodamage so as to identify strategies for minimizing its effects on in vivo imaging. 6) To develop new immuno-labeling techniques for both the TEM and the SEM. Last, but by no means least, 7) we plan to identify application areas that our technology can best serve and to seek collaborations that will both benefit from our resources and that will drive our research and development.